Mayr studied medicine in Vienna before being persuaded by Gustav Mahler to pursue a career as a singer. After studying at the Vienna Music Academy for several years, he made his professional opera début to critical acclaim at the Bayreuth Festival in 1902 as Hagen in Wagner's Götterdämmerung. This led to his being engaged as a principal singer at the Vienna Hofoper by Mahler where he enjoyed a highly successful career that lasted for three decades. His first role in Vienna was Silva in Giuseppe Verdi's Ernani. Mayr also sang at the Royal Opera, London from 1911-1913 and again from 1924 (when he made his second début at the house in 1924 in one of his signature roles, Baron Ochs in Der Rosenkavalier) to 1931. He sang for three consecutive seasons at the Metropolitan Opera in New York City, making his Met début as Pogner in Die Meistersinger von Nürnberg in 1927. He was also a mainstay at the Salzburg Festival, appearing every year there from 1921 until his retirement from the stage in 1934.